Current Aging Science - Volume 6, Issue 2, 2013

A redox basis of the increased oxidative protein damage and free radical-mediated desialylation have not been fully elucidated in aging. It is well known that the incidence of several liver diseases increase with age. This original research focuses on protein oxidation mechanisms and protein-bound sialic acid levels in liver tissue of the mimetic aging rats. Injection of D-galactose (60 mg/kg/day) for six weeks to male Sprague-Dawley rats (20-week-old) used to establish mimetic aging model. We investigated the tissue levels of various protein oxidation markers such as protein carbonyl groups, suitable advanced oxidation protein products and protein thiol groups. Our study also covered protein-bound sialic acid in liver tissue of D-galactose-induced aging rats. PCO (Protein Carbonyl Groups), P-OOH (Protein Hydroperoxides) and AOPP (Advanced Oxidation Protein Products) levels in aging rats were significantly higher compared to young control groups. On the other hand, P-SH (Protein Thiol Groups) levels were not found to be different between two groups. SA (Sialic Acid) levels in D-galactose-induced aging rats were significantly lower compared to control groups. Our results demonstrated greater susceptibility to hepatic oxidative protein damage and desialylation of hepatocellular proteins in Dgalactose- induced aging rats. These molecular mechanisms may be operative in the many age-related liver diseases, which are pertinent to increased oxidative stress and altered redox homeostasis.

The effect of treatment with melatonin was investigated in a rat model of Alzheimer’s disease (AD) involving a single intra-hippocampal injection of amyloid peptide Aβ1-42. Thirty days after this injection immunohistochemical analysis revealed significant increases of both S-100β and NFκB in cortex and hippocampus of treated animals. Levels of synaptophysin were depressed following treatment and this was confirmed by Western blotting. Histopathological studies revealed a diminution of neuronal cell number in the CA3 area of the hippocampus. Behaviorally, the rate of learning escape from electroshock using a maze box was diminished in Aβ-treated mice. Another group of Aβ treated also received an oral gavage of 0.5 mg/kg melatonin on each of the 30 days between Aβ treatment and sacrifice. The effect of this repeated melatonin exposure was to reverse Aβ-induced changes in CA3 cell number and S-100 levels. The increased cerebral content of NF-κB and the behavioral changes caused by Aβ treatment were partially reversed by melatonin. However, melatonin administration had no effect on the reduced level of synaptophysin in Aβ-treated mice. Overall, these findings suggest that melatonin may exert a potentially beneficial effect upon the progression of AD.

Dementia of the Alzheimer type is the most common form of dementia affecting mostly the elderly population. It is a progressive and fatal neurodegenerative disorder with characteristic neuropathology and clinical symptomology. In the coming years, the number of individuals with Alzheimer’s disease (AD) will increase as the elderly population worldwide is expected to grow significantly thus putting an added strain on national health care systems as well as caregivers who will inevitably carry most of the care burden. Thus it has been suggested that early intervention strategies which delay or halt the disease progression will have a strong impact on clinical outcomes. Changes in lifestyle habits such as diet modification or supplementation have been indicated as probable protective factors for a number of chronic conditions including AD. Particular attention has recently been devoted to the Mediterranean diet which is rich in the antioxidants Vitamins C and E, polyunsaturated fatty acids and polyphenolic compounds. Several in vitro, animal and population-based studies reported a positive effect between adherence to a Mediterranean diet and AD prevention, although contrasting views remain. This review will focus on the latest developments and findings in the ongoing research investigating the relationship between Mediterranean diet and its major constituents in AD onset and progression.

We have investigated age-related changes in the reliability of glutathione-related antioxidant enzyme defense in monkeys that differ in adaptive behavior. Activities of gluthatione reductase (GR), glutathione peroxidase (GSH-Px), and gluthatione-S-transferase (GST) and also lipid peroxidation products (TBARS) under basal conditions and under acute psycho-emotional stress were evaluated in erythrocytes of young (6-8 years) and old (20-27 years) female rhesus monkeys with depression-like and standard (control) behavior. We have found that young animals with depression-like behavior, in comparison with young monkeys of standard behavior, demonstrated higher activity of GR in basal conditions and no significant changes in response to acute immobilization stress. With aging the activity of GR increased in monkeys with standard behavior in basal conditions but retained the ability to increase under acute stress. At the same time during aging in monkeys with depression-like behavior GR activity did not undergo significant changes in basal conditions and did not change in response to acute stress. Moreover, old animals with depression-like behavior demonstrated reduced activity of GSH-Px. More pronounced disturbances in GR and GSH-Px activities in animals with depression-like behavior evidence a more marked decrease in the reliability of antioxidant enzyme defense of cells and lead to activation of lipid peroxidation that may be considered as an important factor of aging. Thus, age-related dysfunctions of the antioxidant enzyme system correlate with the type of adaptive behavior characteristic of animals.

Background: Leukoraraiosis is worldwide considered as a part of the normal aging process, although it is strongly associated with dementia and other disabilities. The pathogenesis of leukoaraiosis still has not been thoroughly acknowledged, even though chronic ischemia with consequent arteriolosclerosis probably due to endothelial dysfunction has been suggested. Treatment focuses on prevention of lesion formation and progression by aggressive control of risk factors, which should begin at an early age and continue on regular basis. Aim of our protocol is to evaluate the effect of long-term oral administration of high-dose L-arginine (6 g/day at least for 24 months) on white matter lesions and neurological and cognitive functions. Materials and Methods: Patients affected by mild to moderate leukoaraiosis will be enrolled in the study. After a complete neurovascular assessment (i.e. accurate blood test examinations, Echocardiography, Doppler ultrasound of the neck and peripheral arteries), they will undergo MRI, specific neuropsychological tests and gait analysis. Patients will be evaluated at baseline, at 6, 12, 18 and 24 month-follow up. Statistical Analysis will be performed using the software R. A significant level of P<0.05 will be set for all the tests. Preliminary Data: Two of the 4 patients currently enrolled in the study presented a mild improvement in cognitive function. Discussion: Because of its high prevalence in over-65-year-old subjects, we hypothesized that treatment with 6 gr of Larginine, as supplementary dietary option, could be helpful in patients affected by leukoaraiosis to improve the cognitive and gait impairment often observed in these subjects (as demonstrated by the LADIS study).

Habitual physical activity and exercise are associated with the mortality rate and significantly contribute to the prevention and/or amelioration of aging-related diseases including metabolic disorders, atherosclerosis, cancer, and dementia. Sirtuins are NAD+-dependent histone deacetylases that have emerged as key regulators of many functions including metabolism, cell growth and apoptosis, as well as control of the aging process. Recent studies have demonstrated that some types of exercise affect the expression and activity of sirtuins in several tissues. This review focuses on the effects of exercise on sirtuins and also their putative role with regard to the effects of exercise on preventing aging- related diseases.

In this study, the performance of a group of 20 physically active older adults was compared with that of a group of 20 sedentary healthy older adults while performing a series of cognitive tasks. These tasks were designed to assess processes that deteriorate most with age, namely executive control (assessed with the Wisconsin Card Sorting Task) and processing speed (simple and choice reaction time tasks). A repetition priming task that does not decline with age, involving attended and unattended picture outlines at encoding, was also included as a control task. The results show that a physically active lifestyle has a positive influence on executive control, processing speed, and controlled processing. As expected, a physically active lifestyle did not enhance repetition priming for attended stimuli, nor did it produce priming for unattended stimuli at encoding. Both groups exhibited robust priming for attended stimuli and no priming for unattended ones. Executive control functions are of vital importance for independent living in old age. These results have practical implications for enhancing the cognitive processes that decline most in old age. Promoting a physically active lifestyle throughout adulthood could significantly reduce the decline of effortful executive control functions in old age.

Oxidative stress plays an important role in aging. Effects of several antioxidants on age-related oxidative stress have been investigated. Carnosine (CAR) and betaine have antioxidant actions. The combination of CAR with vitamin E (CAR+E) increases its antioxidant efficiency. We investigated the effects of CAR+E and betaine treatments on oxidative and antioxidative status in liver, heart and brain tissues of aged rats. Experiments were carried out on young (5 months) and aged (22 months) male Wistar rats. Aged rats were given CAR (250 mg/kg; i.p.; 5 days per week) and vitamin E (200 mg/kg; i.m.; twice per week) or betaine (1% w/v) for two months. Malondialdehyde (MDA) and diene conjugate (DC) levels and antioxidants were measured. MDA and DC levels were higher in tissues of aged rats than young rats. Glutathione (GSH) levels decreased in liver, but not heart and brain. There were no changes in vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in tissues of aged rats. CAR+E treatment was observed to decrease MDA and DC levels in tissues of aged rats. However, betaine decreased only hepatic MDA and DC levels. Both CAR+E and betaine increased hepatic GSH and vitamin E levels, but these treatments did not affect antioxidant enzyme activities. These results suggest that CAR+E treatment seems to be useful to decrease oxidative stress in liver, heart and brain tissues, but betaine is only effective in liver tissue of aged rats.

Gel-Repairer is a biomaterial composed of Polydeoxyribonucleotides (Pdrn), Heat Shock Proteins (Hsps) and a thickening substance. It works as a local mesenchymal stem cells (MSCs) stimulator, finally generating connective tissue renewal. Our research is within the field of regenerative medicine and has historically built its foundation from the studies carried out on non-vital amnion and placental membranes. Our end point is the activation and stimulation of the local mesenchymal stem cells (MSCs) for the structural recovery of the joint involved in the degenerative process. Since 2003, we have been applying the Gel Repairer over morethan 1200 patients, most of them elderly, affected by Degenerative Joint Disease (DJD). After 10 years of clinical experience, the results are really impressive, including the absence of toxicity, adverse reactions or side effects. Our clinical findings allowed the presentation of a clinical preliminary study performed on a large group of patients from 2003 to 2009 and recently published [1]. The following article is aimed at looking into the mechanism of action of the Joint Self-Repair procedure; furthermore some new technical opportunities are presented on tissue engineering advances in this fast evolving sector.